Suppressive effects of -Hederin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated murine Cyp1a-1 expression in the mouse hepatoma Hepa-1c1c7 cells

Abstract

Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with α-Hederin to assess the role of α-Hederin in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and Cyp1a-1 protein. When α-Hederin and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by α-Hederin in a dose-dependent manner. TCDD-induced Cyp1a-1 protein and mRNA levels were markedly reduced in the concomitant treatment of TCDD and α-Hederin consistent with EROD activity. Electrophoretic mobility shift assay using nuclear extraction of cells revealed that α-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene. These results suggest that the suppressive effect of α-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor.